This invention relates to materials for use in prosthetic vascular grafts, vascular structures made form such materials, and to the art of using such materials and structures.
The art of preparing prosthetic devices made of various plastics for use as vascular grafts is well developed. Prior art workers have widely investigated plastic substances for such use. One of the common problems encountered by them in the implantation of a vascular prosthesis is the failure of the graft by reason of thrombosis at the site of the graft. Among the causes of arterial graft failures due to arterial thrombosis are biological incompatibility and insufficient flow or velocity through the graft caused by an inadequate inflow and/or outflow and turbulence at the site of the graft. To overcome such baleful influences it would be desirable to lend thromboresistant properties to the bloodstream-graft interface.
Much work has been done on the problem by prior art workers. In 1961 Gott and his co-workers determined that graphite placed in the bloodstream reduced thrombosis. See Gott, B. L., et al, "The Coating of Intravascular Plastic Prosthesis with Colloidal Graphite", Surgery 50:382, 1961. The authors attributed such thromboresistance to the electro-negative conductivity of the graphite. The further suggested that the conductivity of graphite dissipates a positive charge and that the bloodstream-graphite interface possesses a negative charge. This concept was subsequently confirmed by others
The significance is that cellular blood elements, as well as fibrinogen and platelets, are known to be negatively charged at the normal pH in the blood. Natural intima (the natural bloodstream lining) is negative in charge with respect to the adventitia, and it is generally thought that this relative negativity plays a significant role in natural anti-thrombogenesis. These concepts are treated in greater detail in the following treatises.
Leininger, R. I. Surface effects in blood-plastic compatibility. Chapter in Biophysical Mechanisms in Vascular Homeostasis and Intravascular Thrombosis (ed. P. N. Sawyer), Appleton-Century-Crofts, New York, 1965, pp 288-294. PA1 Milligan, H. L., Davis, J. W., and Edmark, K. W. The search for the nonthrombogenic property of colloidal graphite. J. Biomed. Mater. Res., 4:121, 170. PA1 Gott, V. L., Whiffen, J. D., Dutton, R. C., Leininger, R. I., and Young, W. P. Biophysical studies on various graphite-benzalkonium-heparin surfaces. Chapter in Biophysical Mechanisms in Vascular Homeostasis and Intravascular Thrombosis (Ed. P. N. Sawyer), Appleton-Century-Crofts, New York, 1965, pp 297-305. PA1 Sawyer, P. N., Brattain, W. H., and Boddy, P. J. Electrochemical criteria in the choice of materials used in vascular prostheses. Chapter in Biophysical Mechanisms in Vascular Homeostasis and Intravascular Thrombosis (Ed. P. N. Sawyer), Appleton-Century-Crofts, New York, 1965, pp 337-348. PA1 Sawyer, P. N. and Pate, J. W. Bioelectric phenomena in intravascular thrombosis. Am. J. Physiol., 175:103, 1953.
As appears from the references, as early as 1953 Sawyer and Pate reported that clotting is caused by a reversal of the normally negative charge on the intima with respect to the adventitia. In 1965 Leininger verbalized the idea that to prevent the deposition of blood elements on vessel walls the prosthetic should have a negative charge.
Over the years attempts were made to provide prosthetic vascular grafts with a negative charge, with varying degrees of success of lack of it. Pure graphite devices have been used, but they have the disadvantages of being rigid and so their use is extremely limited, e.g., mechanical components of heart valves. Coated flexible tubes have been tried experimentally with only temporary success. The general problem is that in use the bloodstream leaches graphite from the graphite-treated vascular prosthetic and thrombosis thereafter develops. Fracture from manipulation of the rigid graphite lining on the flexible substrate form emboli in the bloodstream, presenting further complications.
Although there existed a need and desire for a vascular prosthetic device having graphite permanently bound to the prosthetic, particularly in flexible vascular grafts, no one in the prior art succeeded in devising a satisfactory solution.
It is, therefore, seen that a longstanding, but un-met, need for a negatively charged plastic prosthetic that will not leach out the graphite existed at the time of the making of this invention, notwithstanding the attention given to the problem by a number of gifted researchers.